Thiophene ring-opening reactions IV. Facile generation of novel ethyl 4-hydroxy-6-thioxonicotinate─1,3,4- thiadiazoline hybrids

: A set of triethylammonium 4-oxo-6-pyridinethiolate–1,3,4-thiadiazoline hybrids (3a-e) were prepared via the reaction of ethyl 2-chloro-6-cyclopropyl-3- nitro-4-oxothieno[2,3-b]pyridine- 5-carboxylate (2) with the appropriate thiobenzoyl- hydrazide (1a-e) in acetonitrile and triethylamine. These hybrids were readily converted, under neutral mild conditions, into the corresponding 4-hydroxy-6-thioxopyridine –thiadiazoline hybrids (5a-e). The structures of the latter set are supported by HRMS, 1H NMR and 13C NMR spectral data and further confirmed by single-crystal X-ray diffraction studies. Alkylation of these hybrids in the presence of triethylamine occurred exclusively at the 6-thioxosulfur, yielding the respective 6-sulfanyl derivatives (6a-c).

Thiophene Ring-Opening Reactions III: One-Pot Synthesis and Antitumor Activity of 1,3,4-Thiadiazoline–Benzothiazolo[3,2-b]pyridazine Hybrids

Introduction: The preparation of model 6-chloro-5-nitrothieno[2,3-c]pyridazines incorporating (2'-halo-5'-nitrophenyl) entity is described. Interaction of these substrates with N'-(aryl)benzothiohydrazides, in the presence of triethylamine, followed a formal [4+1] annulation, furnishing the respective 1,3,4-thiadiazoline–benzothiazolo [3,2-b]pyridazine hybrids directly. This one-pot synthesis implies thiophene ring-opening and two consecutive intramolecular cyclizations. The structures of the synthesized new hybrids are supported by MS, NMR, and IR spectral data and further confirmed by single-crystal X-ray diffraction. These hybrids exhibit antiproliferative activity with notable selectivity against solid tumor cell lines (IC50: 4-18 μM). Aims: This study aimed at exploring the scope and applicability of thiophene ring-opening reaction towards the synthesis of new thiadiazoline–[fused]tricyclic conjugates. Background: α-Chloro-β-nitrothienopyridazine underwent ring-opening upon reacting with N'-(aryl)benzothiohydrazides generating 1,3,4-thiadiazoline–benzothiazolo[3,2-b]pyridazines. Objective: This new thiophene ring-opening reaction is applied to the one-pot synthesis of thiadiazoline–benzothiazolo[3,2-b]pyridazine couples. Method: A direct interaction of α-chloro-β-nitrothienopyridazine with N'-(aryl)benzothiohydrazide at room temperature for 1-2 h occurred. Result: α-Chloro-β-nitrothieno[2,3-c]pyridazines are suitable substrates for the facile synthesis of thiadiazoline–benzothiazolo[3,2-b]pyridazine hybrids. Conclusion: This novel ring-opening reaction proceeds via formal [4+1] annulation and provides a versatile approach to various conjugated and/or fused five-membered heterocycles.

Selective Oxidation of Clopidogrel by Peroxymonosulfate (PMS) and Sodium Halide (NaX) System: An NMR Study

A selective transformation of clopidogrel hydrogen sulfate (CLP) by reactive halogen species (HOX) generated from peroxymonosulfate (PMS) and sodium halide (NaX) is described. Other sustainable oxidants as well as different solvents have also been investigated. As result of this study, for each sodium salt the reaction conditions were optimized, and four different degradation products were formed. Three products were halogenated at C-2 on the thiophene ring and have concomitant functional transformation, such as N-oxide in the piperidine group. A halogenated endo-iminium product was also observed. With this condition, a fast preparation of known endo-iminium clopidogrel impurity (new counterion) was reported as well. The progress of the reaction was monitored using nuclear magnetic resonance spectroscopy as an analytical tool and all the products were characterized by 1D-, 2D-NMR and HRMS.

Analysis of Biphenylene and Benzo{3,4}cyclobuta{1,2-c}thiophene Molecular Orbital Structure using the Huckel Method

The Huckel method is an old fashion method to predict the molecular orbital and energies of  electrons in a conjugated molecule. Although Huckel`s theory`s approximations are relatively crude, its general results are still reasonable compared to the advanced computing method and experimental results for many molecules. This paper describes the Huckel calculation of biphenylene and benzo{3,4}cyclobuta{1,2-c}thiophene using the HuLis software. The benzo{3,4}cyclobuta{1,2-c}thiophene is a derivative of biphenylene, in which case one of the benzene rings is replaced by a thiophene ring. This change produces new electronic properties that are interesting to study. This work focused on calculating those molecules on energy levels diagrams, linear combination coefficient of molecular orbitals, molecular orbital shape, energy gap, resonance energy, bond-order, bond length, and charge distribution (π electron population). Besides, we calculate the harmonic oscillator measure of aromaticity (HOMA) parameter to study the Huckel method`s validity.

Novel Mononuclear Divalent Zinc, Cadmium and Mercury Complexes of Tridentate Hydrazone Ended by Thiophene Ring

New hydrazone derivative, namely (Z)-4-((3-cyano-4,6-dimethyl pyridine-2-yl)amino)-N'-(thiophen-2-ylmethylene)benzohydrazide (H2BTH) and its mononuclear Zn(II), Cd(II) and Hg(II) complexes were prepared and characterized by conventional measurements. Infrared spectral data confirmed that the hydrazone coordinates to metal ion as neutral NS or NO. The structure of Cd(II) complex was further studied by x-ray powder diffraction. The density functional theory (DFT) based quantum chemical calculations were accomplished at B3LYP/6-level of theory andMuilikan atomic charge in a companion with global and local reactivities and various energetic values have been calculated at the selected atoms, and the reactive sites have been assigned on the surface of the molecules through molecular electrostatic potential (MEP) map. TGA and DrTGA were used to establish some compounds' thermal stability, and the kinetic parameters of activation such as ΔG*, ΔH*, and ΔS* were determined. Moreover, all investigated compounds were screened for antimicrobial and DNA binding activities.

Thiophene-Based Trimers and Their Bioapplications: An Overview

Certainly, the success of polythiophenes is due in the first place to their outstanding electronic properties and superior processability. Nevertheless, there are additional reasons that contribute to arouse the scientific interest around these materials. Among these, the large variety of chemical modifications that is possible to perform on the thiophene ring is a precious aspect. In particular, a turning point was marked by the diffusion of synthetic strategies for the preparation of terthiophenes: the vast richness of approaches today available for the easy customization of these structures allows the finetuning of their chemical, physical, and optical properties. Therefore, terthiophene derivatives have become an extremely versatile class of compounds both for direct application or for the preparation of electronic functional polymers. Moreover, their biocompatibility and ease of functionalization make them appealing for biology and medical research, as it testifies to the blossoming of studies in these fields in which they are involved. It is thus with the willingness to guide the reader through all the possibilities offered by these structures that this review elucidates the synthetic methods and describes the full chemical variety of terthiophenes and their derivatives. In the final part, an in-depth presentation of their numerous bioapplications intends to provide a complete picture of the state of the art.

Design, Molecular Docking, Synthesis and Biological Evaluation of 4, 5-Substituted 1, 2, 3-Triazoles as Anti-bacterial Agents

Newer antibacterial agents are needed to combat the growing bacterial infections. Triazoles are one of the leading and most sought out nucleus amongst the heterocyclic rings in the drug world. 1, 2, 3-Triazoles are synthesized by Click Chemistry of alkynes with azides. A synergistic effect is observed when the triazoles are combined with other heterocycles. They also exhibit diversified therapeutic activities like anti-viral, anti-bacterial, anti-diabetic, anti-tubercular, anti-inflam-matory, antihypertensive etc which makes Triazoles an interesting molecule for the researchers to work on. In the current study, we combined 1,2, 3-triazoles with thiophene ring system to get synergistic antibacterial activity. Here, 12 derivatives of 4, 5-substituted-1, 2, 3-Triazoles were subjected to in silico docking studies on Biotin ligase protein (PDB ID: 3V7R). The compounds that showed the best results were synthesized. The newly synthesized derivatives were characterized by using IR, H1 NMR and Mass spectrum. All the synthesized derivatives were evaluated for antibacterial activity against Gram-negative bacteria (E. coli and P. aerugenosa) and gram-positive bacteria (B. subtilis and S. aureus). The compounds showed moderate to good activity, which was comparable to that of the standard Streptomycin drug.